INTRACELLULAR CALCIUM REGULATION OF CHANNEL AND RECEPTOR EXPRESSION IN THE PLASMALEMMA - POTENTIAL SITES OF SENSITIVITY ALONG THE PATHWAYS LINKING TRANSCRIPTION, TRANSLATION, AND INSERTION

Nervous system development is ''activity dependent''-activation of neu rons controls their development, which controls their activation patte rns, which will then influence their further development, and so on. A critical issue is thus the regulation of channel and receptor express ion. For nerve cells, the presence of specialized Ca2+-permeable chann els in the surface membrane provides a direct link between electrical activity and the intracellular Ca2+ ion concentration ([Ca2+](i)), and in many instances [Ca2+](i) is thought to link membrane activation an d internal biosynthesis. In this context, Ca2+-permeable channels func tion as ''activity sensors,'' transducing membrane activation by admit ting Ca2+ rapidly, locally, and proportionately. In this review, I con sider the potential of [Ca2+](i) to regulate channel and receptor expr ession. I emphasize mechanisms by which the Ca2+ concentration of the cytosol and/or the Ca2+ concentrations of membrane-delimited Ca2+ sequ estering organelles may influence biosynthetic processes. Here, I use ''expression'' in the most general sense of referring to the number an d location of functional channels and receptors in the plasmalemma; re gulation of expression is not limited to transcriptional regulation, b ut further encompasses translational and posttranslational processes. At the core is the notion of regulation by patterned oscillations in c ytosolic [Ca2+], and, in a synchronous or contrapuntal manner, filling and depletion of a series of Ca2+-sequestering organelles-nuclear env elope, endoplasmic reticulum, Golgi, trans-Golgi network, and secretor y vesicles-that all also have critical roles in biosynthesis of membra ne proteins. These structures provide both an internal Ca2+ regulation and distribution system, and a scaffold for synthesis, targeting, and insertion of channels and receptors. (C) 1998 John Wiley & Sons, Inc.